NO GROWTH-STIMULATION OF HETEROTRANSPLANTED HUMAN TESTICULAR CANCER CELL-LINES BY RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF)

Abstract

Hematopoietic growth factors such as granulocyte (G)- and granulocyte-macrophage (GM) colony-stimulating factor (CSF) are currently used as adjunct treatment for cancer chemotherapy in order to ameliorate neutropenia. The current investigation presented here focused on the in vivo effects of GM-CSF on two heterotransplanted human testicular cancer cell lines in a nude mouse model. GM-CSF was applied to tumor bearing mice in a dose range of 3 x 10(5) to 3 x 10(7) U/kg per day i.v. for 14 consecutive days. For all concentrations of GM-CSF a reduction of the tumor volume compared to untreated tumor bearing control mice was noted. The largest retardation of tumor growth was seen at the end of the experiments at day 30 with 3 x 10(7) U/kg of GM-CSF with a relative tumor volume of 72% +/- 8% for cell line H 12.1 and 73.5 +/- 9% for cell line H23.1 in comparison to untreated tumor bearing control mice. No side effects of GM-CSF application such as weight loss or fever were observed. Serum tumor necrosis factor (TNF) levels in mice treated with GM-CSF were considerably lower compared to untreated tumor carrying control animals. No growth stimulation of heterotransplanted human testicular germ cell tumors by GM-CSF has been observed in this nude mice tumor model. Further studies will have to demonstrate, whether GM-CSF is even possibly able to exhibit an antitumor effect. With respect to tumor cell kinetics the clinical use of GM-CSF in the treatment of patients with testicular cancer can be regarded as safe.